1590. Updated Aminoglycoside (AG) MIC Breakpoints (BP) to Minimize Adverse Events and Improve Outcome: Impact on Susceptibility (S) Rates

Abstract

BackgroundIn 2016 USCAST, the National Advisory Committee (NAC) for the United States (US) to EUCAST, undertook the re-evaluation of the in vitro susceptibility (AST) test interpretive criteria (IC) for gentamicin (GM), tobramycin (TO) and amikacin (AK) against Enterobacteriaceae (ENT), P. aeruginosa (PSA) and S. aureus (SA) based on an analysis of contemporary microbiology and PK/PD data. In 2019 USCAST posted the third version (www.uscast.org) of AG IC document and CLSI and EUCAST has published AG IC in CLSI M100-S29 and EUCAST v 9.0 documents. USCAST ICs for S were generally lower than those proposed by CLSI for all organism/drug combinations. PK/PD emphasized high, extended interval dosing (5 renal function groups) to reduce nephro-vestibular toxicity and a stasis exposure endpoint. Here, we evaluate the impact on S rates for US AST data that these IC changes created.MethodsClinical isolates from 2010 to 2018 US SENTRY Program (reference broth microdilution AST) were analyzed for S based on current and previous IC values. AG results for GM, TO and AK were evaluated against 66,280 ENT, 13,959 PSA and 51,950 SA. Benchmark S data for meropenem, cefepime, piperacillin–tazobactam and new AG, plazomicin (PZM) were included as well as ESBL and carbapenem-resistant ENT (CRE; 805 isolates).ResultsS rates for ENT as determined by USCAST IC were reduced by 4.2/1.2/3.1% for AK/GM/TO (CLSI) and by 3.3% for AK (EUCAST); no S rate difference for GM and TO as determined by USCAST/EUCAST. For PSA, S decreased by 46.8/6.2% for AK/TO (EUCAST) and 51.6/6.2% (CLSI). S for SA vs. GM declined by only 0.2% (CLSI). No AG IC could be calculated/offered for Acinetobacter or GM X PSA or AM/TO X SA. Best S overall coverage X ESBL (99.2%) or CRE (97.2%) isolates was by PZM.ConclusionUSCAST IC updates for AG lead to reduced values for some organism/drug combinations among ENT and PSA compared with those proposed elsewhere. The USCAST-recommended ICs were based on achieving AUC/MIC ratio target associated with net bacterial stasis. Given the assumption of AG combination therapy, stasis was considered a reasonable endpoint when evaluating AG ICs to improve both safety and efficacy. Some organism X drug exposures could not be calculated and lower IC for pneumonia isolates (GM, TO) was recommended. Disclosures All authors: No reported disclosures.